Dr Seung Seo Lee BSc, MSc, PhD

Lecturer in Chemical Biology

Dr Seung Seo Lee is a chemical biologist, and his research has been focused on the chemical biology of proteins and enzymes involved in post-translational modification of proteins, with a long standing interest in the structure, function and mechanism of ubiquitin and its related enzymes, and carbohydrate processing enzymes. Recently he is using his expertise in chemical biology to tackle antibiotic resistant microbes, particularly methicillin resistant Staphylococcus aureus.

Dr Seung Lee obtained his BSc and MSc in chemistry from Seoul National University in Seoul, Korea. He then worked in the pharmaceutical industry before starting his doctoral study in chemistry at University of British Columbia in Vancouver, Canada. He obtained his PhD under the supervision of Professor Stephen G Withers, studying the reaction mechanism of glycan processing enzymes. For his postdoctoral studies, he expanded his skillset to directed evolution techniques with Dr Florian Hollfelder in Department of Biochemistry at University of Cambridge and synthetic carbohydrate chemistry with Professor David R Bundle in the Department of Chemistry at University of Alberta. He then joined Professor Benjamin G Davis' group, working on various projects of chemical biology involving enzymes. In October 2012 he was appointed as a lecturer in Chemistry at University of Southampton.

Ubiquitination is one of the most important post translational modifications of proteins. Ubiquitin (Ub), a small polypetide consisting of 76 amino acid residues, may be attached to or removed from the substrate protein depending on the cellular demand. The best studied function of ubiquitination is the ubiquitin-mediated proteasomal degradation of proteins, which enables to control protein levels, thereby affecting associated cellular processes. In addition to protein degradation, ubiquitination is also directly implicated in various cellular signalling events, including immunity, T-lymphocyte control and cell division among others. It has been known that the impairment in the ubiquitin system results in various diseases including cancer, cardiovascular disease, and neurodegenerative disorder. Functional studies of ubiquitin have been hampered by the complex nature of poly-ubiquitin structure. We are developing a novel method to synthesise specific poly-ubiquitin selectively by chemical means for functional studies. Also, we are developing specific inhibitors for the immune modulation by ubiquitin.

2. Methicillin resistant Staphylococcus aureus

Multidrug-resistant Staphylococcus aureus (MDRSA), including a vancomycin resistant variant of methicillin-resistant Staphylococcus aureus, is a serious concern in patient safety and healthcare system. Antibiotic resistance in Staphylococcus aureus (SA) results from mutations and the acquisition of foreign resistant genes. Resistance is expressed in such a way that SA alters the antibiotic target proteins or antibiotic itself, or pumps out the antibiotic via the efflux mechanism. Thus, existing antibiotics are no longer effective due to these mechanisms. Therefore, it is considered that novel targets and different class of antibiotic molecules are urgently needed to tackle the MDRSA pandemic. We have identified a novel target for therapeutic intervention. This target is not affected by the methicillin resistance mechanism and has a great potential to cleanly eradicate the bacteria in the host. We are expecting our research will lead to a clue to tackling this worldwide problem.

3. Glycan processing enzyme

Glycosylation is a key biological process, which is often associated with many diseases. We are interested in analysis of reactions catalysed by enzymes involved in both anabolic and catabolic glycan processing in pathogenic processes of Mycobacterium tuberculosis. Based on this analysis, small molecules that can modulate in vivo activity of enzymes can be effectively designed and synthesized, which have a potential for therapeutics. The approach involves:

A.the synthesis of small molecules that will report necessary information upon reaction with enzymes.

B.analysis of results from enzymatic reaction with the aid of computations.

C3.design and synthesis of specific inhibitors of enzymes based on analysis of enzyme reactions. This research also has a potential of leading to the development of biosensors and biomarkers.

Our primary target in M. tuberculosis is glycan processing enzymes involved in the biosynthesis of methylglucose lipopolysaccharide. We are currently synthesising a variety of potential substrates and inhibitors for these enzymes. As a spin-off project of glycan processing enzymes, we are involved in the development of biocatalyst for the synthesis of complex glycans.